人原癌基因c-fms启动子E1上游富含鸟嘌呤DNA片段d(G_(3)AG_(3)T_(2)G_(3)A_(2)G_(3))体外形成的G-四链体之间自发进行构型转换  

In vitro spontaneous conformational transitions between G-quadruplexes formed by the guanine-rich DNA fragment d(G_(3)AG_(3)T_(2)G_(3)A_(2)G_(3))upstream of promoter E1 in the human proto-oncogene c-fms

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作  者:刘芷玥 景海涛 朱婷 付文强 张钠 胡文萱 LIU Zhiyue;JING Haitao;ZHU Ting;FU Wenqiang;ZHANG Na;HU Wenxuan(Institutes of Physical Science and Information Technology,Anhui University,Hefei 230601,China;High Magnetic Field Laboratory,Hefei Institutes of Physical Science,Chinese Academy of Sciences,Hefei 230031,China)

机构地区:[1]安徽大学物质科学与信息技术研究院,合肥230601 [2]中国科学院合肥物质科学研究院强磁场科学中心,合肥230031

出  处:《生物学杂志》2025年第2期7-14,共8页Journal of Biology

基  金:国家自然科学基金联合项目(U1932157)。

摘  要:F3g是源自人类原癌基因c-fms启动子E1上游的DNA短链片段d(G_(3)AG_(3)T_(2)G_(3)A_(2)G_(3))。核磁共振研究发现,F3g在近生理的K+溶液中能折叠成两种不同的G-四链体结构,并且观察到这两种G-四链体结构间存在自发转化过程。随后,利用核磁共振、圆二色谱与凝胶电泳等多种技术共同验证表明:处于动力学有利的Form 1结构为非全平行型的两层G-四链体结构;而处于热力学稳定的Form 2结构则形成了由两个全平行型三层G-四链体相互堆叠的结构。研究结果为进一步理解人类原癌基因c-fms的表达调控以及相关疾病的靶向治疗提供了一定的参考与理论基础。F3g is a short DNA fragment,d(G_(3)AG_(3)T_(2)G_(3)A_(2)G_(3)),locating upstream of promoter E1 in the human proto-oncogene c-fms.Nuclear magnetic resonance(NMR)studies have revealed that,in near-physiological K+solutions,F3g folds into two distinct G-quadruplex structures with a spontaneous folding topology switch.Subsequent validations using a combination of techniques including NMR,CD,and PAGE have demonstrated that the kinetically favored Form 1 structure was a non-parallel two-tetrad G-quadruplex,while the thermodynamically stable Form 2 structure consisted of a stack of two parallel three-tetrad G-quadruplexes.These findings provided insights and a theoretical basis for further understanding the expression regulation of the human proto-oncogene c-fms and the targeted treatment of related diseases.

关 键 词:人类原癌基因c-fms DNA G-四链体 自发结构转换 核磁共振 圆二色谱 

分 类 号:Q754[生物学—分子生物学]

 

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